Mórdicus, Arturo Costa Álvarez’s alter ego. New contributions to an archive of the debate on language in the 1920s

El artículo presenta y describe un conjunto de textos aparecidos en los periódicos "El Argentino" y "El Hogar" bajo el seudónimo de Mórdicus, detrás del cual puede identificarse la figura de Arturo Costa Álvarez. Una prueba decisiva para esta identificación reside en el hallazgo de un conjunto de manuscritos de artículos inéditos pertenecientes a la misma firma dentro del legado de este autor, preservado en la Sala Museo de la Biblioteca Pública de la Universidad Nacional de La Plata que lleva su nombre, cuya transcripción se ofrece como parte de este trabajo. En estos textos puede observarse cómo Costa Álvarez refuerza desde otra posición, provista por el seudónimo y caracterizada justamente por la mordacidad de su discurso, aquello que procuraban hacer sus intervenciones en la época a través de periódicos y revistas como "Valoraciones", "El Hogar" y "El Argentino" entre otros; esto es, no solo establecerse como voz autorizada en el debate glotopolítico de su época, sino también defender ese lugar contra el surgimiento y avance, en los años veinte, del Instituto de Filología, institución con directores procedentes del Centro de Estudios Históricos de Madrid.The following paper aims at presenting and describing some texts published in the newspapers "El Argentino" and "El Hogar" under the pseudonym “Mórdicus”, behind which we have identified the figure of Arturo Costa Álvarez. A decisive proof for this identification lies in the finding of a set of manuscripts for unpublished articles also signed by the abovementioned pseudonym among the legacy of this author, preserved by the Biblioteca Pública de la Universidad Nacional de La Plata, in a section bearing Costa Álvarez’s name. A transcription of these manuscripts is offered in the appendix to the following paper. In the texts signed by Mórdicus, we can see how Costa Álvarez reinforces what his contemporary interventions in magazines, journals and newspapers at that time aimed at –that is, not only to establish itself as an authorized voice in the glotopolitical debate of its time, but also to defend that place against the emergence and advancement, in the 1920s, of the Instituto de Filología, an institution with directors from the Center for Historical Studies from Madrid. He does this from an alternative position, provided by the pseudonym and pervaded with mordacity.Facultad de Humanidades y Ciencias de la Educació

RGD_PLGA Nanoparticles with Docetaxel: A Route for Improving Drug Efficiency and Reducing Toxicity in Breast Cancer Treatment

Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects

White-to-brown transdifferentiation of omental adipocytes in patients affected by pheochromocytoma

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Association between proton-pump inhibitors (PPI) and metronomic capecitabine (MCAP) as salvage treatment for patients with advanced gastro-intestinal tumoursa. A randomized phase II study

Background: Several researches have shown that acidification of tumor microenvironment is the basis for tumor invasiveness, ability to metastasize S382 Abstracts and cytotoxic agents resistance; therefore proton pump inhibitors (PPI) could significantly increase the chemosensitivity. In our retrospective work we have investigated the role of capecitabine (mCAP) at metronomic dosage of 1500 mg/die as salvage chemotherapy in patients with metastatic colorectal cancer, showing a moderately activity and well tolerability. In this prospective study we evaluated safety and activity of mCAP in the advanced gastro-intestinal patients and the putative chemosensitizing activity of a specific PPI (Rabeprazole) in association to this therap

Health-Literate Healthcare Organizations and Quality of Care in Hospitals: A Cross-Sectional Study Conducted in Tuscany

The concept of Health-Literate Healthcare Organization (HLHO) concerns the strategies by which healthcare organizations make it easier for people to navigate, understand, and use information and services to take care of their health. The aims of this study were to validate the HLHO-10 questionnaire in the Italian language; to measure the degree of implementation of the 10 attributes of HLHOs in a sample of hospitals placed in Tuscany; and to assess the association between the degree of implementation of the 10 attributes of HLHOs and the perceived quality of care. This was a cross-sectional study where data were collected using a self-administered questionnaire including three sections: a descriptive section, a section focused on the perceived quality, and the Italian version of the HLHO-10 questionnaire. A total amount of 405 healthcare managers answered the questionnaire (54.9%). The analysis shows that the HLHO score is significantly associated with the type of hospitals: accredited private hospitals have higher HLHO scores. Moreover, the perceived quality increases with the increasing of the HLHO score, with the highest coefficient for local public hospitals. In conclusion, Organizational Health Literacy culture should be an integral element for the management to improve the quality of care

Combination therapy of high-dose rabeprazole plus metronomic capecitabine in advanced gastrointestinal cancer: a randomized phase II trial

Abstract: Background: In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose tomodulate tumormicroenvironment acidification thus restoring chemotherapeutic sensitivity. This is the first trial to study activity and safety of repurposing high dose rabeprazole combined with metronomic capecitabine (mCAP). Methods: A phase II study in which patients with gastrointestinal cancer, refractory to standard treatments, who had a life expectancy >3 months, were blind randomized 1:1 to mCAP, 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg bid, three days a week. The primary endpoint was 3-months progression-free survival (PFS). The secondary endpoints were clinical benefit (CB) and overall survival (OS). Safety and plasma concentrations of capecitabine and its metabolites (50-DFUR and 5-FU) were also evaluated. Results: Sixty-seven (median age 69 years; 63% male; 84% colorectal cancer, 76% ECOG-PS 1; 84% pretreated with two or more lines of chemotherapy) out of 90 patients screened for eligibility, were randomized to receive mCAP+rabeprazole (n = 32) vs. mCAP (n = 35). All patients were evaluable for response. No significant dierence between mCAP+rabeprazole vs. mCAP, in terms of 3-months PFS rate (HR = 1.43, 95%CI 0.53–3.85; p = 0.477), median PFS (HR = 1.22, 95%CI 0.75–2.00, p = 0.420), CB (RR = 0.85, 95%CI 0.29–2.44; p = 0.786) and median OS (HR = 0.89, 95%CI 0.54–1.48; p = 0.664) was observed. However, a 3-year OS rate of 10% and 12% was reported in the mCAP-rabeprazole and mCAP groups, respectively. Overall, no grade 3 or 4 toxicity occurred but grade 1 or 2 adverse event of any type were more frequently in the mCAP+rabeprazole group than in the mCAP (OR 2.83, 95%CI 1.03–7.79; p = 0.043). Finally, there was not statistically significant dierence in the plasma concentration of capecitabine and its metabolites between the two groups. Conclusions: Although the adjunct of high dose rabeprazole to mCAP was not shown to aect mCAP activity, as PPI are being investigated worldwide as drugs to be repositioned in cancer treatment and also considering the limited sample size as well as the favorable safety profile of the combination in the present study, further clinical investigations are desirable

WAT to BAT transdifferentiation of omental fat in adult humans affected by pheochromocytomas

In small mammals and to some extent also in humans, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT) are contained together in discrete locations at subcutaneous or visceral level forming a multi-depots organ [1]. We have recently described paucilocular cells immunoreactive for uncoupling protein 1 (UCP1-ir) as morphological marker of WAT-BAT transformation in the adipose organ of cold-exposed mice (hyper-adrenergic stimulation) [2]. In this study, we examined biopsies of omental WAT depot, in 20 controls and in 12 patients affected by pheochromocytomas used as model of adrenergic stimulation in humans. Histological examination was performed by light microscopy, immunohistochemistry and Electron Microscopy. qPCR was carried out to asses relative expression of “brown” genes. Control tissues were all formed by unilocular UCP1-negative adipocytes. Half of the omental fat samples from pheochromocytomas showed UCP1-ir multilocular cells forming BAT-islands among WAT. Several UCP1-ir paucilocular cells were also detected. Higher density of TH-ir fibres and capillaries were found in the transformed tissues. Ultrastructural examination, highlighted poorly differentiated cells in pericapillary position with features similar to those identified in supraclavicular human BAT [3]. In light of the protective role exerted by BAT against the development of obesity and other metabolic diseases, WAT to BAT plasticity could be an important target for the development of therapeutic strategies in the treatment of obesity and type II diabetes in humans

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription